Abstract
Von Hippel-Lindau (VHL) disease is the main cause of inherited kidney cancer and the model of tumoral angiogenesis. This rare syndrome is caused by germline mutations of the VHL tumor-suppressor gene that predispose to the development of a panel of highly vascularized tumors. Main manifestations include CNS and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. The VHL gene plays a major role in regulation of the oxygen-sensing pathway by targeting the hypoxia-inducible factor HIF for degradation in proteasome. Somatic inactivation of the VHL gene occurs also in most sporadic RCC. Recent progress are pawing the way for the development of antiangiogenic targeted therapies that have already shown promising results in metastatic sporadic RCC.
MeSH terms
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Animals
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Central Nervous System Neoplasms / diagnosis
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Central Nervous System Neoplasms / genetics
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Central Nervous System Neoplasms / therapy
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Genes, Tumor Suppressor / physiology
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Germ-Line Mutation / genetics
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Hemangioblastoma / diagnosis
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Hemangioblastoma / genetics
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Hemangioblastoma / therapy
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Humans
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Kidney Neoplasms / genetics
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Kidney Neoplasms / pathology
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Kidney Neoplasms / therapy
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Mutation / genetics
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Neovascularization, Pathologic / genetics*
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / therapy
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Pheochromocytoma / genetics
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Pheochromocytoma / pathology
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Pheochromocytoma / therapy
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Polycythemia / genetics
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Retinal Neoplasms / genetics
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Retinal Neoplasms / pathology
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Retinal Neoplasms / therapy
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Von Hippel-Lindau Tumor Suppressor Protein / genetics*
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von Hippel-Lindau Disease / diagnosis
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von Hippel-Lindau Disease / genetics*
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von Hippel-Lindau Disease / therapy
Substances
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Von Hippel-Lindau Tumor Suppressor Protein